Understanding the molecular mechanisms of the novel Bioherbicide Myrigalone A

George Heslop-Harrison

Research output: ThesisDoctoral Thesis


Plant derived allelochemicals represent a class of natural products that regulate the growth and survival of neighbouring plants and microorganisms. Understanding how allelochemicals function to
regulate plant responses may help provide valuable new approaches to better control plant function. One such allelochemical, Myrigalone A (MyA) is produced by Myrica gale (sweet gale) and inhibits seed germination and seedling growth. The underlying mechanism for this effect however
remains unclear. Here we investigate MyA using the model organism Dictyostelium discoideum, to show that it reduces cell proliferation and delays multicellular development. An unbiased genomewide mutant library screen identified a mechanism for this effect, through inhibition of the
homologue of the plant ethylene synthesis protein, 1-aminocyclopropane-1-carboxylic acid oxidase (ACO). Gene ablation of ACO mimics the MyA-dependent delay in development, which is partially restored by exogenous ethylene. In this model, MyA reduces ethylene production, suggesting a
mechanism for MyA through inhibiting ACO activity. Molecular modelling using the plant (Petunia) ACO protein predicts that MyA directly inhibits ACO activity through binding within the substrate binding pocket. In A._thaliana seedlings, MyA and established ACO inhibitors (AIB and POA) reduced
root and hypocotyl extension, and blocked ethylene-dependent root hair production. Finally, in silico binding analysis coupled with high through-put compound screening identified a range of novel substituted cyclic diones providing highly potent ACO inhibition in D. discoideum and A._thaliana.
Thus, we identify a molecular mechanism for the allelochemical MyA in reducing ethylene biosynthesis through direct inhibition of ACO to block ethylene production and suggest MyA related compounds that show promise as use in an agricultural or horticultural settings.
Original languageEnglish
Awarding Institution
  • Royal Holloway, University of London
  • Williams, Robin, Supervisor
  • Leubner, Gerhard, Advisor
Thesis sponsors
Publication statusUnpublished - 30 Jun 2023

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